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Systematic review and meta-analysis of the effect of iron chelation therapy on overall survival and disease progression in patients with lower-risk myelodysplastic syndromes

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Abstract

The impact of iron chelation therapy (ICT) on overall survival (OS) and progression to acute myeloid leukemia (AML) in patients with iron overload and International Prognostic Scoring System low- or intermediate-risk myelodysplastic syndromes (MDS) is not well understood. We conducted a systematic review and meta-analysis of published studies of ICT in patients with MDS to better elucidate these relationships. We searched PubMed, EMBASE, Cochrane databases, and the World Health Organization Clinical Trial Registry for studies reporting the impact of ICT on OS in patients with low- or intermediate-risk MDS. Studies were examined for demographics, effect measures, and potential bias risk. Fixed and random-effects models were used to calculate adjusted OS and adjusted hazards ratio (aHR) estimates, respectively, among the different studies. Nine observational studies (four prospective and five retrospective) were identified. For patients with MDS, ICT was associated with an overall lower risk of mortality compared with no ICT (aHR 0.42; 95% confidence interval (CI) 0.28–0.62; P < 0.01); however, there was significant heterogeneity across the studies. In studies reporting progression to AML, ICT was not associated with decreased risk of progression (odds ratio 0.68; 95% CI 0.31–1.43; P < 0.030). This systematic review and meta-analysis of nine nonrandomized trials demonstrated significant reduction in risk of mortality in patients with iron overload and low- or intermediate-risk MDS treated with ICT; however, a causal relationship cannot be established. Randomized, controlled trials are needed to more definitively evaluate the relationship between ICT and survival in patients with iron overload and low- or intermediate-risk MDS.

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Acknowledgements

The authors were responsible for all content and editorial decisions, and received no honoraria related to the development of this manuscript. The authors appreciate the generous support of Dr. Heather Leitch from the University of British Columbia and Dr. Ivo Abraham from the University of Arizona for their sharing of additional data beyond the information provided in their published papers. Editorial support in the preparation of this manuscript was provided by Susan DePetris, PhD, of Phase Five Communications, and was supported by Novartis Pharmaceuticals Corporation.

Funding

Editorial support in the preparation of this manuscript was provided by Phase Five Communications, and was funded by Novartis Pharmaceuticals Corporation.

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Authors and Affiliations

  1. Yale University School of Medicine and Yale Cancer Center, Smilow Cancer Hospital at Yale New Haven, New Haven, CT, USA

    Amer M. Zeidan & Smith Giri

  2. Yale School of Public Health, New Haven, CT, USA

    Michelle DeVeaux

  3. Cardeza Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA, USA

    Samir K. Ballas

  4. University of Maryland School of Medicine, Baltimore, MD, USA

    Vu H. Duong

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  1. Amer M. Zeidan
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Contributions

AMZ and VHD independently performed the database search and agreed on the final study selection. SG and MD extracted data from the selected studies in duplicate using a standardized data-extraction form. They also assessed the quality of the included studies. AMZ performed a cross-check for data accuracy. All authors contributed to the writing of the manuscript, and all authors approved the final manuscript.

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Correspondence to Amer M. Zeidan.

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Conflict of interest

Amer M. Zeidan has received research funding from Celgene, Incyte, Takeda, Pfizer, ADC Therapeutics, Medimmune, Trovagene, AbbVie, and Merck; he has consulted for Agios, AbbVie, Otsuka, Pfizer, Gilead, Celgene, Ariad, Incyte, Takeda, and Novartis; and he has served as a speaker for Takeda. Samir K. Ballas has served on the speakers bureau for Novartis and has received honoraria from Novartis. Smith Giri, Michelle DeVeaux, and Vu H. Duong declare that they have no conflict of interest.

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Zeidan, A.M., Giri, S., DeVeaux, M. et al. Systematic review and meta-analysis of the effect of iron chelation therapy on overall survival and disease progression in patients with lower-risk myelodysplastic syndromes. Ann Hematol 98, 339–350 (2019). https://doi.org/10.1007/s00277-018-3539-7

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